Purpose: 1. To identify the receptors on malaria parasites for red cell invasion and on infected red cells for adhesion to endothelium and to placenta. 2. Identify cross-reactive epitopes on the domain of the variant antigen on the red cell surface and test the vaccine in Aotus monkeys for protecting against virulent P. falciparum. Accomplishments during the year:1.Identification of a new receptor on P. falciparum malaria parasites for binding to red cells. The only other receptor identified to date is EBA-175 which has not been highly effective alone as a vaccine. Perhaps combining different receptors in one vaccine may improve vaccine efficacy.2.The domain on the variant antigen for binding chondroitin sulfate A in placenta has been identified. As the binding of infected red cells in placenta is associated with fetal and newborn mortality, blocking this with a vaccine may reduce disease. Antibodies to this domain appear to be cross-reactive to parasites from around the world. We are working on this domain as a vaccine candidate.3.The first vaccine trial against one of the domain of the variant antigen (CIDR1) on the red cell surface for binding endothelium has been used in a vaccine in Aotus monkeys that was highly successful.4.Monoclonal antibodies to CIDR1 used for vaccine development in (3) are cross-reactive with multiple strains of P. falciparum.